ROLE OF DIETARY ADIPOSE AND ENDOGENOUSLY SYNTHESIZED FATTY ACIDS IN PATHOGENESIS OF ALCOHOLIC FATTY LIVER

ROLE OF DIETARY ADIPOSE AND ENDOGENOUSLY SYNTHESIZED FATTY ACIDS IN PATHOGENESIS OF ALCOHOLIC FATTY LIVER
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DOI:
10.1172/jci105323
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发表时间:
1966-01-01
影响因子:
15.9
通讯作者:
DECARLI, LM
DECARLI, LM
中科院分区:
医学1区
文献类型:
--
作者:
LIEBER, CS;SPRITZ, N;DECARLI, LM

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在大鼠中,一个大剂量的乙醇(7.5克/公斤)产生中度的脂肪酸肝蓄积类似的脂肪组织;相反,在长期乙醇摄入后,脂肪肝更明显,脂肪酸组成不同于贮库脂肪。大鼠给予24天的乙醇与低脂饮食(2%的热量)有一个亚油酸浓度在肝脏甘油三酯的五分之一的脂肪组织,然而,50%以上的棕榈酸,内源性合成的脂肪酸。在给予酒精和含脂肪饮食(43%的卡路里)的大鼠中,肝脏甘油三酯中积累的脂肪酸含有大量的膳食脂肪酸(月桂酸酯加肉豆蔻酸酯或亚麻酸酯),而这些脂肪酸在给予“预标记”脂肪组织时,发现肝脏甘油三酯中的含量远低于贮库中的含量。尽管乙醇摄入量相同,但给予含碳水化合物而非脂肪的等热量饮食的大鼠脂肪变性明显较少。24天后,2%脂肪饲料组的总肝脏脂质升高了1.5倍,而43%脂肪饲料组升高了2.6倍;相应的甘油三酯变化分别为2.6倍和6.3倍。而乙醇对肠内棕榈酸酯-C14吸收或肝脏静脉注射乳糜微粒-C14的摄取没有明显影响,棕榈酸酯-C14插管后2至6小时或乳糜微粒-C14注射后3小时,肝脏脂质标记增强。这些研究表明,酒精给药后肝脏甘油三酯中脂肪酸蓄积的来源和程度取决于酒精摄入的剂量和持续时间以及相关饮食的脂肪含量。
In rats, one large dose of ethanol (7.5 g per kg) produced moderate hepatic accumulation of fatty acids resembling those of adipose tissue; in contrast, after prolonged ethanol intake, fatty liver was more pronounced and had a fatty acid composition different from depot fats. Rats given 24 days of ethanol with low-fat diets (2% of calories) had a linoleate concentration in hepatic triglycerides one-fifth that of adipose tissue with, however, 50% more palmitate, an endogenously synthesized fatty acid. In rats given alcohol with fat-containing diets (43% of calories), fatty acids accumulating in the liver triglycerides had a large component of dietary fatty acids (either laurate plus myristate or linolenate), whereas these fatty acids when administered to "prelabel" adipose tissue were found to be much less abundant in liver triglycerides than in depots. Despite the same ethanol intake, significantly less steatosis developed in rats given isocaloric diets containing carbohydrate instead of fat. After 24 days, the rise in total hepatic lipids was 1.5-fold on the 2% fat diet compared to 2.6-fold on the 43% fat diet; corresponding triglyceride changes were 2.6- and 6.3-fold respectively. Whereas ethanol had no apparent effect on intestinal palmitate-C14 absorption or uptake by the liver of chylomicron-C14 administered intravenously, hepatic lipid labeling was enhanced 2 to 6 hours after palmitate-C14 intubation or 3 hours after chylomicron-C14 injection. These studies indicate that the source and the magnitude of the fatty acids accumulating in hepatic triglycerides after alcohol administration depend on the dose and duration of alcohol intake as well as the fat content of the associated diet.